Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

Cutaneous squamous cell carcinoma tumor accrual rates in immunosuppressed patients with autoimmune and inflammatory conditions: A retrospective cohort study.

BACKGROUND: Immunosuppression is a known risk factor for the development of cutaneous squamous cell carcinoma (CSCC), especially in solid organ transplant recipients and chronic lymphocytic leukemia. However, this risk is less well defined in autoimmune and inflammatory conditions. OBJECTIVE: Assess the impact that disease-type, duration of immunosuppression, and systemic medications have on CSCC accrual rates, defined as the number of CSCCs a patient develops per year, in autoimmune and inflammatory conditions. METHODS: Retrospective review of 94 immunosuppressed (rheumatoid arthritis: 31[33.0%], inflammatory bowel disease: 17[18.1%], psoriasis: 11[11.7%], autoimmune other (AO): 24[25.5%], inflammatory other: 21[22.3%]) and 188 immunocompetent controls to identify all primary, invasive CSCCs diagnosed from 2010 to 2020. RESULTS: Immunosuppressed patients had higher CSCC accrual rates than immunocompetent controls (0.44 ± 0.36): total cohort (0.82 ± 0.95, P < .01), rheumatoid arthritis (0.88 ± 1.10, P < .01), inflammatory bowel disease (0.94 ± 0.88, P < .01), psoriasis (1.06 ± 1.58, P < .01), AO (0.72 ± 0.56, P < .01), and inflammatory other (0.72 ± 0.61, P < .01). There was an association between increased tumor accrual rates and exposure to systemic medications including, immunomodulators, tumor necrosis factor-alpha inhibitors, non-tumor necrosis factor inhibitor biologics, and corticosteroids, but not with number of systemic medication class exposures or duration of immunosuppression. LIMITATIONS: Retrospective, singlecenter study. CONCLUSION: Patients with autoimmune and inflammatory conditions accrue CSCCs at higher rates than immunocompetent patients.

A multicenter real-world analysis of risk factors, therapeutics, and outcomes of patients with metastatic basal cell carcinoma.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is rare and there are limited data regarding patient and tumor risk factors, optimal treatments, and disease prognosis. OBJECTIVE: To assess patient and tumor characteristics, therapeutics, and outcomes of mBCC stratified by location of metastasis. METHODS: Retrospective cohort study of 53 patients with mBCC treated at 4 large academic centers in Boston, Massachusetts; Philadelphia, Pennsylvania; and Cleveland, Ohio between January 1, 2005 and December 31, 2021. RESULTS: A total of 53 patients with mBCC were identified across 4 centers, 22 (42%) of whom had mBCC with spread limited to lymph nodes and 31 (58%) patients with distant organ spread (with or without lymph node involvement). Overall, half (n = 11) of patients with nodal metastasis achieved complete remission of disease, compared with just 1 (3%) patient with distant metastasis. The 5-year survival for nodal and distant metastatic patients was 89.3% and 61.0%, respectively. LIMITATIONS: Small sample size due to disease rarity. CONCLUSIONS AND RELEVANCE: Patients with nodal disease are more likely to have disease remission whereas patients with distant metastasis are more likely to have persistent disease and die from their disease. However, 5-year survival rates exceed 50%, even for stage IV disease.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Patterns of major cutaneous surgeries and reconstructions in patients with cutaneous squamous cell carcinoma in the USA.

Aim: Since use of major cutaneous surgeries/reconstructions among patients with cutaneous squamous cell carcinoma (CSCC) is not well described, we sought to quantify major cutaneous surgeries/reconstructions among patients with CSCC who were newly diagnosed and for those treated with systemic therapy, stratified by immune status. Methods: We used the Optum® Clinformatics® Data Mart database (2013-2020) and Kaplan-Meier estimators to assess risk of surgeries/reconstructions. Results: 450,803 patients were identified with an incident CSCC diagnosis, including 4111 patients with CSCC who initiated systemic therapy. The respective 7-year risks of major cutaneous surgeries/reconstructions were 10.9% (95% CI: 10.7-11.0) and 21.8% (95% CI: 17.6-25.8). Overall risk of major cutaneous surgeries/reconstructions was higher in patients who were immunocompromised than those who were immunocompetent. Conclusion: Approximately one in nine patients with CSCC will undergo ≥1 major cutaneous surgeries/reconstructions within 7 years of diagnosis; the risk increases in patients who initiate systemic therapy and among those who are immunocompromised.

Cutaneous squamous cell carcinoma (CSCC) is one of the two most common cancers, and numbers of new cases are increasing each year by 3­7%. A small number of advanced cases require systemic treatments (drugs given by mouth or injection), such as chemotherapy or immunotherapy. Patients with CSCC may require major skin surgeries and reconstructions. Little is known about how these skin procedures are used to treat patients with CSCC, particularly those with a weakened immune system. This analysis used USA insurance data of patients from 2013 to 2020 to assess how they were treated with surgeries, based on patients' immune status and whether they had started systemic treatment for CSCC. Among the 450,803 patients identified with a new CSCC diagnosis, the chances of having a procedure over a 7-year period was 10.9% (around one in nine). For 4111 patients with CSCC who started systemic therapy, this was 21.8% (around one in five). The chances of having a procedure were also significantly higher in patients with a weakened immune system (14.0%, around one in seven), compared with those without. However, this study was potentially limited by the following: the study population might not fully represent the CSCC population, the risk of surgery might be underestimated and information about patients' tumors (e.g., staging) was lacking. These results suggest there is an unmet need for systemic treatments that can reduce the burden of skin surgeries and reconstructions in CSCC.

Conversion of a Validated Melanoma Risk Stratification Tool Into a Tablet-Based Patient Questionnaire for Targeted Melanoma Screening in Primary Care Settings: A Pilot Study.

BACKGROUND: Risk stratification can identify individuals in primary care settings who are at increased risk of developing melanoma. OBJECTIVE: Converting and implementing a validated risk stratification tool as a patient self-administered tablet-based survey. METHODS: Mackie risk stratification tool was transformed into a patient questionnaire. The questionnaire was completed in academic dermatologist practices by patients and dermatologists and revised to optimize sensitivity and specificity using physician assessment as gold standard. The optimized survey was administered before routine primary care visits during 2019 to 2021. High-risk patients were referred to dermatology. The number needed to screen (NNS), sensitivity, specificity, positive predictive value, and negative predictive value to identify a melanoma were calculated. RESULTS: Of the 7,893 respondents, 5,842 (74%) and 2,051 (26%) patients were categorized as low-risk and high-risk population, respectively. The NNS to identify 1 melanoma was 64 in the high-risk population. CONCLUSION: Incorporating self-administered patient-risk stratification tools in primary care settings can identify high-risk individuals for targeted melanoma screening. Further studies are needed to optimize specificity and sensitivity in more targeted populations.

Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study.

BACKGROUND: We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival. METHODS: This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing. FINDINGS: Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need. FUNDING: Regeneron Pharmaceuticals and Sanofi.

No difference in survival for primary cutaneous Merkel cell carcinoma after Mohs micrographic surgery and wide local excision.

BACKGROUND: The preferred treatment for clinically node-negative Merkel cell carcinoma (MCC) is surgical excision in conjunction with sentinel lymph node biopsy. There is limited large-scale research on survival outcomes by surgical approach for management of the primary tumor. OBJECTIVE: To compare overall and MCC-specific survival outcomes in clinically and pathologically, node-negative MCC patients treated with wide-local excision (WLE) and Mohs micrographic surgery (MMS) in a nationally representative sample. METHODS: Overall and MCC-specific survival outcomes for primary MCC tumors contained in the SEER (Surveillance, Epidemiology, and End Results)-18 database from 1989 to 2015 were stratified by surgical modality and analyzed via competing risk analysis. RESULTS: A total of 2359 US adults with MCC were included in the analysis. For overall and MCC-specific survival, there was no significant difference in survival outcomes between WLE and MMS on multivariable analysis (hazard ratio, 1.04 [95% CI, 0.88-1.22]; subdistribution hazard ratio, 0.76 [95% CI, 0.53-1.09]). Sentinel lymph node biopsy was associated with improved overall survival and MCC-specific survival. LIMITATIONS: Retrospective design of SEER and the lack of covariates such as comorbidities and immunostaining. CONCLUSION: There is no survival disadvantage for MMS compared to WLE as the surgical modality for primary cutaneous MCC. Sentinel lymph node biopsy should be coordinated prior to MMS.

Improved Margin Control of Microcystic Adnexal Carcinoma After Mohs Micrographic Surgery Compared With Wide Local Excision.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a locally aggressive and deeply infiltrative cutaneous tumor primarily treated with excision; however, there are limited data comparing outcomes by surgical approach. OBJECTIVE: To compare surgical outcomes of MAC treated with Mohs micrographic surgery (MMS) and wide local excision (WLE). METHODS: A 27-year retrospective cohort study of primary MAC was performed. Surgical (i.e. margin status after resection) and recurrence outcomes (including local recurrence [LR], nodal metastases [NM], and distance metastases [DM]) were analyzed by type of surgical approach (MMS and WLE). RESULTS: Sixty-nine MACs were included, of which 34 (49.3%) were treated with MMS and 35 (50.7%) with WLE. All MMS-treated tumors had negative margins after the first surgery attempt. Twenty-one (60.0%) tumors treated with WLE had positive margins after the first surgical attempt and required additional procedures. More tumors treated with WLE developed LR, NM, or DM, although this did not meet statistical significance. LIMITATIONS: Retrospective single institution study. CONCLUSION: Greater than half of MAC tumors treated with WLE had positive margins after the initial surgery and required multiple procedures for complete removal. Real-time complete margin assessment is important for this locally aggressive and infiltrative tumor.

Education and Perspectives on the Use of Oral Skin Cancer Chemoprophylaxis: A Cross-Sectional Survey of Current Fellows in Mohs Micrographic Surgery & Dermatologic Oncology.

BACKGROUND: According to the curriculum guidelines of the Accreditation Council of Graduate Medical Education and the American Board of Dermatology, Mohs micrographic surgery & dermatologic oncology (MSDO) fellows must demonstrate competency in the use of oral skin cancer chemoprophylaxis. The current level of education in this area is unknown. OBJECTIVE: To characterize oral skin cancer chemoprophylaxis education for acitretin and nicotinamide among current MSDO fellows and to compare the clinical indications felt most appropriate for prescribing to a previously published expert consensus. METHODS: An electronic survey was distributed to all active MSDO fellows by the American College of Mohs Surgery. RESULTS: Responses were received from 63 (69.2%) MSDO fellows. Twenty (31.7%) and 37 (58.7%) fellows reported receiving fellowship training on acitretin and nicotinamide, respectively. Fifty-seven (90.5%) intend to prescribe chemoprophylaxis after training. Sixteen (28.1%) and 43 (75.4%) report feeling very comfortable prescribing acitretin and nicotinamide, respectively. Fellow concordance with a previously published expert consensus opinion on appropriate prescribing indications is variable. Forty-one (65.1%) indicated that additional education would increase the likelihood to prescribe after training. CONCLUSION: Although most MSDO fellows intend to prescribe oral skin cancer chemoprophylaxis, a standardized curriculum may promote increased use and concordance with expert consensus recommendations.

Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer.

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.

Higher metastasis and death rates in cutaneous squamous cell carcinomas with lymphovascular invasion.

BACKGROUND: Lymphovascular invasion (LVI) is an aggressive histologic finding but is excluded from current staging systems due to its lack of demonstrated independent prognostic significance. OBJECTIVE: To evaluate the impact of LVI on cutaneous squamous cell carcinoma tumor outcomes. METHODS: In total, 10,707 cutaneous squamous cell carcinoma tumors from a 20-year, retrospective, multicenter cohort were stratified by the presence (LVI+) or absence (LVI-) of LVI. Outcomes (local recurrence, in-transit metastasis, nodal metastasis, disease-specific death) were compared based on low (Brigham and Women's Hospital [BWH] stage T1/T2a) and high (BWH T2b/T3) tumor stages. RESULTS: Of the 10,707 tumors, 78 had LVI. The analysis of low-stage BWH tumors showed the LVI+ group had a significantly higher 5-year cumulative incidence of local recurrence (LVI+: 12.3%; LVI-: 1.1%; P < .01), metastasis (LVI+: 4.2%; LVI-: 0.4%; P < .01), and disease-specific death (LVI+: 16.2%; LVI-: 0.4%; P < .01). The analysis of BWH high-stage tumors showed the LVI+ group maintained a higher 5-year cumulative incidence of metastasis (LVI+: 28.5%; LVI-: 16.8%; P = .06) and disease-specific death (LVI+: 25.3%; LVI-: 13.9%; P = .03), however, there was no difference in local recurrence (LVI+: 16.3%; LVI-: 15.8%; P = .11). LIMITATIONS: Retrospective study design. CONCLUSION: LVI+ cutaneous squamous cell carcinomas have higher rates of metastasis and death at 5 years. Future staging systems should consider incorporating LVI.

Identifying Brigham and Women's Hospital stage T2a cutaneous squamous cell carcinomas at risk of poor outcomes.

BACKGROUND: Although most of the poor outcomes with cutaneous squamous cell carcinoma (CSCC) occur in high-stage tumors, 26% of nodal metastases and 8% of disease-specific deaths develop in Brigham and Women's Hospital (BWH) T2a tumors. OBJECTIVE: To determine risk factors associated with poor outcomes (nodal metastasis, distant metastases, and disease-specific deaths) in BWH T2a CSCC. METHODS: A 17-year retrospective multi-institutional cohort study of primary CSCC BWH T2a tumors. A predictive model based on tumor characteristics was developed to identify those at higher risk of poor outcomes. RESULTS: Presence of 1 major criterion (primary tumor diameter ≥40 mm, invasion depth beyond subcutaneous fat, poor differentiation, or large-caliber perineural invasion) and ≥ 1 minor criterion (invasion depth in subcutaneous fat, moderate differentiation, small-caliber perineural invasion, or lymphovascular invasion) was most predictive of developing poor outcomes (area under the curve, 0.53; C-statistic, 0.60). This model has a sensitivity of 7.7%, specificity of 97.4%, and a positive and negative predictive value of 33.3% and 86.1%, respectively. The 5-year cumulative incidence of poor outcomes in these tumors is 8.0% (95% CI, 5.1-13.7) compared to 2.8% (95% CI, 1.9-4.1) in other T2a tumors (sub-hazard ratio, 3.0; 95% CI, 1.5-5.8). LIMITATIONS: Multi-institutional cohort study was not externally validated. CONCLUSIONS: BWH T2a-high CSCCs have an 8% chance of developing poor outcomes.

Immune status does not independently influence cutaneous squamous cell carcinoma metastasis and death when stratified by tumor stage: A dual-center retrospective cohort analysis of primary N0 disease.

BACKGROUND: Although immunocompromised patients have a higher risk of developing cutaneous squamous cell carcinomas, it is unknown whether immune status is an independent risk factor for poor outcomes. OBJECTIVE: To compare cutaneous squamous cell carcinoma outcomes in immunocompromised and immunocompetent patients when controlling for T-stage. METHODS: We performed a retrospective cohort study at 2 tertiary care centers, examining 989 primary tumors from 814 immunocompromised patients (solid organ transplant: 259 [31.7%], chronic lymphocytic leukemia: 113 [13.9%]) and 6608 tumors from 4198 immunocompetent patients. Our primary outcome was the composite of disease-specific death or tumor metastasis ("poor outcomes"). RESULTS: Immunocompromised patients had 50% more high T-stage tumors (ie, Brigham and Women's Hospital stage T2b and T3), than immunocompetent patients (3.3% vs 4.9%, respectively; P < .001). Significant predictors of poor outcomes included tumor stage (sub hazards ratio [SHR], 14.8 for high T-stage tumors; 95% confidence interval [CI], 8.0-27.6; P < .001) and male sex (SHR, 2.3; 95% CI, 1.4-3.8; P = .002). Immune status was not a significant predictor (SHR, 1.04; 95% CI, 0.69-1.6; P = .85). LIMITATIONS: This study is retrospective. CONCLUSION: Although immunocompromised patients had 50% more high T-stage tumors than immunocompetent patients, immunocompromised patients had a similar chance of metastasis and disease-specific death when adjusting for T-stage in our cohort of primary tumors.

Adjuvant radiation following clear margin resection of high T-stage cutaneous squamous cell carcinoma halves the risk of local and locoregional recurrence: A dual-center retrospective study.

BACKGROUND: Although adjuvant radiation (ART) following clear margin surgery is recommended for select high-risk cutaneous squamous cell carcinomas, efficacy data are limited. OBJECTIVE: To evaluate the impact of ART on outcomes following clear margin surgery for high T-stage cutaneous squamous cell carcinomas. METHODS: A 20-year retrospective cohort study at 2 academic centers of high T-stage cutaneous squamous cell carcinomas (Brigham and Women's Hospital T2b or T3) with negative histologic margins post resection. Local recurrence (LR) and locoregional recurrence (LRR) were compared by whether tumors received ART or observation. RESULTS: A total of 508 tumors were included, of which 96 underwent ART (ART+). ART+ had a lower 5-year cumulative incidence of LR (ART+, 3.6% [95% CI, 1.6%-7.7%] vs ART-, 8.7% [95% CI, 6.3%-12.0%]) and LRR (ART+, 7.5% [95% CI, 4.4%-11.9%] vs ART-, 15.3% [95% CI, 11.9%-22.1%]). Recurrent tumors ≥6 cm or Brigham and Women's Hospital T3 tumors were classified as high-risk due to a higher 5-year cumulative incidence of LRR (High-risk, 26.3% [95% CI, 19.0%-35.7%]). High-risk tumors treated with ART had a lower 5-year cumulative incidence of LRR (ART+, 17.2% [95% CI, 11.9%-26.4%] vs ART-, 31.0% [95% CI, 26.1%-40.8%]). LIMITATIONS: Retrospective design, heterogeneous population, variations in radiation protocols. CONCLUSION: ART following clear margin surgery for high T-stage cutaneous squamous cell carcinomas resulted in half the risk of LR and LRR.

Hedgehog pathway inhibitor real-world treatment patterns in patients with basal cell carcinoma: a claims-based analysis.

Aims: To examine real-world treatment patterns for Hedgehog pathway inhibitors (HHIs) for the treatment of advanced basal cell carcinoma. Patients & methods: HHI initiators between January 2013 and June 2019 were identified from IBM MarketScan® claims data. Time to treatment discontinuation and reinitiation were estimated using Kaplan-Meier methods using a 60-day grace period. Results: Among 526 patients with basal cell carcinoma who initiated an HHI, median time to first discontinuation was 144 days, and risk of discontinuation by 12 months was 88.0%. Probability of reinitiation within 12 months was 19.7%, and median time to second discontinuation was 118 days. Conclusion: HHI discontinuation was common and reinitiation uncommon in clinical practice. Future research should evaluate persistence with recently approved therapies.

This study examined patterns of discontinuation and reinitiation of Hedgehog pathway inhibitors (HHIs) such as vismodegib or sonidegib for patients with basal cell carcinoma, the most common form of skin cancer. Initiation of HHI treatment was identified from prescriptions filled by patients with commercial insurance or Medicare who had basal cell carcinoma. Discontinuation was defined as a gap of more than 60 days without treatment, after drug supply had run out. Among the 526 patients identified, one-half had discontinued HHI treatment within about 5 months and 88% had discontinued treatment within 1 year. Fewer than 20% of patients restarted treatment. Discontinuations are common but restarting treatment is uncommon among patients with basal cell carcinoma treated with HHIs.

Total Margin-Controlled Excision is Superior to Standard Excision for Keratinocyte Carcinoma on the Nose: A Veterans Affairs Nested Cohort Study.

BACKGROUND: Keratinocyte carcinoma (KC), including basal and squamous cell carcinoma, is the most common human malignancy. Limited real-world data have compared surgical outcome or cost between total margin-controlled excision (TMCE) and standard excision (SE), the two most common treatments for invasive KC. We compared reconstruction, margin status, and cost between TMCE and SE for KC on the nose at a Veterans Affairs (VA) healthcare system. METHODS: Randomly selected primary KCs on the nose ≤3 cm that were confined to soft tissue, without nerve or lymphovascular invasion, and treated with SE or TMCE between 2000 and 2010, were assessed. Utilization of flap or graft reconstruction and margin status following all surgical attempts were recorded. Costs were based on Current Procedural Terminology codes standardized to 2019 Medicare payments. RESULTS: Overall, 148 cases were included in each treatment group. Baseline characteristics were similar between groups, although SE tumor median diameter was 1 mm larger. SE was associated with increased utilization of flap or graft reconstruction (odds ratio 2.05, 95% confidence interval 1.16-3.59, p = 0.01). Positive margins were present in 24% of SEs initially and remained positive after the final recorded excision in 9% of cases. No positive final margins were noted in TMCE cases. SE cost per tumor was significantly higher than TMCE ($429.03 ± 143.55; p = 0.003). CONCLUSIONS: Surgical management of KC with SE is associated with increased reconstruction complexity, a significant risk of positive margins, and higher cost compared with TMCE. The 23% risk of positive margins supports National Comprehensive Cancer Network guidelines for the treatment of high-risk KC with TMCE, unless delayed reconstruction is employed.

Assessing the Value of Cemiplimab for Adults With Advanced Cutaneous Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the cost-effectiveness of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC) from a payer perspective in the United States. METHODS: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review, supplemented by expert opinion where necessary. Clinical inputs for cemiplimab were based on individual patient data from a cemiplimab phase 2 single-arm trial (NCT27060498). For SOC, analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via a systematic literature review (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. RESULTS: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio of $99 447 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372 108 and 3.74, respectively. At a willingness-to-pay threshold of $150 000/QALY, the probabilistic sensitivity analysis suggests a 90% probability that cemiplimab is cost-effective compared to SOC. Scenario analyses resulted in incremental cost-effectiveness ratios ranging from $90 590 to $148 738. CONCLUSIONS: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.

Brigham and Women's Hospital tumor classification system for basal cell carcinoma identifies patients with risk of metastasis and death.

BACKGROUND: Despite approximately 4400 locally advanced US cases annually, high-stage basal cell carcinoma (BCC) is ill-defined. OBJECTIVE: To develop a tumor (T) staging system for BCC that will predict metastasis/death and compare its performance with that of the American Joint Committee on Cancer 8th edition (AJCC8) T-staging system. METHODS: Brigham and Women's Hospital (BWH) T staging was developed from a previously published nested cohort of 488 primary BCCs. Tumors were staged via BWH and AJCC8 T-staging systems, and predictions of metastasis and/or death were compared. RESULTS: The BWH and AJCC8 T-staging systems both captured all metastases/deaths in high T stages (BWH, T2; AJCC8, T3/T4). BWH T2 included 54% fewer cases ≥2 cm than AJCC8 T3/T4. BWH had a higher specificity (0.92 vs 0.80; P < .001) and positive predictive value (24% vs 11%, P < .001) for identifying cases at risk for metastasis/death, and the C-statistic was superior for BWH (P < .001). The BWH T2 10-year cumulative incidence of metastasis/death was 37% (95% confidence interval, 21%-60%). LIMITATIONS: Two-center cohort. CONCLUSIONS: BWH and AJCC 8 BCC staging both capture all metastases and deaths in the upper stages. However, BWH staging does so in half the number of cases, thus minimizing inappropriate up-staging. The risk of metastasis or death in BWH T2 BCC is sufficient to warrant surveillance for recurrence and clinical trials of adjuvant therapy.